Bis(4-amino-or 4-substituted amino-3,5-dinitrophenyl) disulfide

ABSTRACT

Bis(hydroxy, amino, or substituted lower alkyl, alkenyl, or alkynylamino-3,5-dinitrophenyl)disulfide prepared by treating 4chloro-3,5-dinitrophenyl thiocyanate with an alkali metal hydroxide, carbonate, acid carbonate, or nitrite, ammonium hydroxide, ammonia, or a primary or secondary lower aliphatic amine; useful as intermediates for the synthesis of herbicides.

United States Patent [191 Cannon [451 Apr. 3, 1973 [54] BIS(4-AMINO-OR4-SUBSTITUTED AMINO-3,5-DINITROPHENYL) DISULFIDE [75] Inventor: WilliamN. Cannon, Greenwood,

Ind.

[73] Assignee: Eli Lilly and Company, Indianapolis,

Ind.

[22] Filed: Apr. 20, 1970 21 Appl. No.: 30,228

[52] U.S. Cl. ..260/576, 260/578, 260/608 [51] Int. Cl ..C07c 87/62 [58]Field of Search ..260/576, 578, 571

[56] References Cited UNITED STATES PATENTS 211968 Soper .L ..260/71FOREIGN PATENTS OR APPLICATIONS 462,497 1/1950 Canada ..260/578 OTHERPUBLICATIONS Theilheimer, Synthetische Methoden der Organischen PrimaryExaminer-Lewis Gotts Assistant Examiner-C. F. Warren AttorneyEveret F.Smith and Walter E. Buting 57] ABSTRACT Bis(hydroxy, amino, orsubstituted lower alkyl, alkenyl, oralkynylamino-3,S-dinitrophenyl)disulfide prepared by treating4-chloro-3,S-dinitrophenyl thiocyanate with an alkali metal hydroxide,carbonate, acid carbonate, or nitrite, ammonium hydroxide, ammonia, or aprimary or secondary lower aliphatic amine; useful as intermediates forthe synthesis of herbicides.

6 Claims, No Drawings BIS(4-AMINO-OR 4-SUBSTITUTED AMINO-3,5-

DINITROPHENYL) DISULFIDE BACKGROUND OF THE INVENTION U.S. Pat. No.3,367,949 describes the preparation of herbicidally activesulfanilamides from the corresponding benzenesulfonyl chloride.

Heretofore the desired 4-substituted-3 ,5 dinitrobenzenesulfonylchloride has been formed from the corresponding potassium sulfonate. Thepotassium sulfonate derivative is obtained by a multi-step synthesiswhich employs l-chloro-2-nitrobenzene as the starting material; proceedsthrough a nitration-sulfonation step utilizing fuming mixednitric-sulfuric acid, and results in the isolation of the potassium saltof 4-chloro- 3,5 -dinitrobenzene sulfonic acid, which is then convertedto the wanted potassium-4-substituted-3,5- dinitrobenzene sulfonate.

The use of fuming mixed nitric-sulfuric acid imposes a burden on theprocess as the disposal of the spent acid is costly and difficultbecause of its dangerous nature. Also, the requirement that thepotassium salt of 4- -chloro-3,S-dinitrobenzene sulfonic acid must be ofbefore proceeding introduces expensive materials handling costs, as wellas opportunities for product losses. Therefore, a more simplified andeconomic process for producing 4-substituted-3,5-dinitrobenzenesulfonylchloride is highly desirable.

SUMMARY This invention provides novel bis(4-substituted-3,5-dinitrophenyl) disulfide compounds, useful as herbicide intermediates.Bis(4-hydroxy-3,S-dinitrophenyl) disulfide is obtained by dinitrophenylthiocyanate with an alkali metal hydroxide, carbonate, acid carbonate,or nitrite in a suitable solvent, such as an ethanol-water mixture, atrefluxing temperature. Bis[4-amino(or substituted amino)-3,5-dinitrophenyl] disulfide is prepared by treating 4-chloro-3,5-dinitrophenyl thiocyanate with ammonia, ammonium hydroxide,or a primary or secondary aliphatic amine in a suitable solvent, such asbenzene, at refluxing temperature. Sulfanilamide herbicides are obtainedfrom the novel compounds of this invention.

DESCRIPTION OF THE PREFERRED EMBODIMENTS This invention relates to novelbis(4-substituted-3,5- dinitrophenyl) disulfides, intermediate compoundsemployed in the synthesis of herbicidally active sulfanilamides, and toa method for their preparation.

It is an object of this invention to provide herbicide intermediateswhich are readily and economically convertible to herbicidally activenovel substituted sulfanilamides described in more detail in U.S. Pat.No. 3,367,949. It is a further object of this invention to provide aprocess by which these intermediates are conveniently prepared.

It has now been discovered that if a substituted phenyl thiocyanate suchas 4-chloro-3,S-dinitrophenyl thiocyanate is reacted with a suitableamine, ammonia, ammonium hydroxide, or an alkali metal base in anappropriate solvent, there is obtained a bis(4-substituted-3,5-dinitrophenyl) disulfide, a herbicide intermediate of valuableproperties. The employment of ammonia,

reacting 4-chloro-3,5-

ammonium hydroxide, or a suitable primary or secondary aliphatic aminein effecting the condensation of two moles of 4-chloro-3,S-dinitrophenylthiocyanate into one mole of bis(4-substituted-3,S-dinitrophenyl)disulfide results in the substitution of an unsubstituted,monosubstituted, or disubstituted amino group for the chlorine in the4-position. The use of an alkali metal base in accomplishing theaforementioned condensation results in the substitution of a hydroxylgroup for the chlorine in the 4-position. The herbicide intermediates ofthis invention are highly reactive and are readily converted toherbicides by relatively simple procedures.

The unexpected formation of the bis(4-substituted- 3,5-dinitrophenyl)disulfides from the corresponding 4- chloro-3,5 -dinitrophenylthiocyanates provides useful compounds which can be employed in themulti-step synthesis of the desired substituted sulfanilamide herbicideobviating the requirement inherent in the prior art processes ofisolating potassium-4-amino(or substituted amino)-3,S-dinitrobenzenesulfonate on the way to 4-amino(or substituted amino)-3,S-dinitrobenzenesulfonyl chloride, which in turn is converted' to thecorresponding herbicidally active sulfanilamide, unsubstituted,monosubstituted, or disubstituted on the sulfonamide nitrogen,respectively.

Another advantage of the novel process of this inventionlies in thenearly quantitative yields of the his disulfide derivatives which areachieved, adding to the economics of preparing herbicidally activesulfonamides from these compounds.

The novel herbicide intermediate compounds of this invention arebis[4-hydroxy(or unsubstituted,- monosubstituted, or disubstitutedamino)-3,5- dinitrophenyl] disulfides having the structure:

l l N02 N02 wherein X is hydroxyl or:

and R and R can be the same or different and are members of the groupconsisting of hydrogen, lower alkyl, lower alkenyl, and lower alkynyl.

The term lower alkyl as used herein means methyl, ethyl, n-propyl,isopropyl, n-butyl, sec-butyl, and t-butyl. The term lower alkenyl asused herein means vinyl, propenyl, ally], l-butenyl, Z-butenyl,3-butenyl, lbutene-Z-yl, 2-butene-3-yl, and l-butene-3-yl. The termlower alkynyl as used herein means ethynyl, lpropynyl, 2-propynyl,l-butynyl, 2-butynyl, S-butynyl, and l-butyn-3-yl.

The useful herbicide intermediates of the present invention can bereadily prepared in a single-step synthesis by heating together in asuitable non-reactive organic solvent such as, for example, benzene,methyl ethyl ketone, N,N-dimethylformamide, or a 3:1 to 1:3ethanol-water solution the known compound 4-chloro- 3,5-dinitrophenylthiocyanate and about a 25 percent molar excess (2 moles of the base, orbasic salt, are required for each mole of thiocyanate) ofa lower alkyl,lower alkenyl, or lower alkynyl primary or secondary amine, ammonia orammonium hydroxide, or an acid carbonate, carbonate, hydroxide, ornitrite or lithium, 5

potassium, sodium or cesium. The reaction is generally conducted in afiveto twentyfold, volume/weight, excess of solvent at atmosphericpressure for from 3 to 24 hours at a temperature of from about 50 C tothe refluxing temperature of the reaction mixture, preferably at therefluxing temperature for from 3 to 6 hours.

Reactant Product NH OH Bis(4-amino-3,5-dinitrophenyl) disulfide NaHCO,Bis( 4-hydroxy-3 ,5 dinitrophenyl) disulfideBis[4-di(n-propyl)arnino-3,5- dinitrophenyl] disulfideBis[4-(butyl)ethylamino-3,5- dinitrophenyl] disulfideBis(4-diallylamino-3,5-

dinitrophenyl) disulfide Bis[4-di(2propynyl)amino-3,5-

dinitrophenyl] disulfide An advantage of the herbicide intermediates ofthe present invention is the simplicity of the procedure by which theycan be converted to herbicidally active sulfanilamides. For instance,bis(4-hydroxy-3,5- dinitrophenyl) disulfide can be treated withphosphorous oxychloride to form bis(4-ch1oro-3,5- dinitrophenyl)disulfide. The bis (4-chloro3,5- dinitrophenyl) disulfide can beconverted to the corresponding bis(4-substitutedamino-3,5-dinitrophenyl) disulfide wherein the 4-substituted aminosubstituent can be a pyrrolidino, piperidino, or morpholino ring as wellas a primary or secondary lower alkyl, alkenyl, or alkynyl amino moiety.

The bis(4-substituted amino -3,5-dinitrophenyl) disulfide can beconverted to the 4-substituted amino- 3,5-dinitrophenyl sulfonylchloride by chlorinating the disulfide derivative. The reactiongenerally is carried out by slurrying the bis(4-substituted amino-3,5-dinitrophenyl) disulfide in from fiveto twentyfold volumes of water andsaturating the aqueous mixture with chlorine, raising the temperature toreflux and continuing the addition of chlorine until the reaction iscomplete. The excess chlorine is removed by vacuum and the reactionproducts extracted into toluene. The desired sulfanilamide herbicide isproduced by reacting the corresponding sulfonyl chloride with ammoniumhydroxide, or a primary amine or a secondary amine, to yield thecorresponding benzenesulfonamide, unsubstituted, monosubstituted, ordisubstituted on the sulfonamide nitrogen atom, respectively. US. Pat.No. 3,367,949 describes in more detail the procedure for convertingbenzenesulfonyl chlorides to herbicidally active sulfanilamides.

The various herbicidally active sulfonamides thus prepared are usefulfor eliminating weed grasses and certain broadleaf weeds selectivelyfrom crop plants such as rice, cotton, soybeans, and corn and theirclose relatives in the plant kingdom.

The method of preparing the herbicide intermediates of this invention isfurther illustrated by the following examples.

EXAMPLE 1 Bis[4-di(n-propyl)amino-3,5-dinitrophenyl] disulfide About10.4 g. (0.04 mole) of 4'chloro-3,5- dinitrophenyl thiocyanate weredissolved in 150 ml. of benzene and 10.1 g. (0.1 mole) ofdi(n-propyl)amine were added with stirring. The mixture warmed up,turned deepred colored, and a precipitate formed and began to separate.The reaction mixture was heated to reflux for 3 hours with stirring. Thereaction mixture was cooled to room temperature and washed 3 times witha 1x volume of water, after which the benzene solution was dried overanhydrous magnesium sulfate, filtered, and, the filtrate evaporated todryness. The residue was recrystallized from percent ethanol to yieldabout 1 1.2 g. of reddish-orange crystals of bis[4-di(n-propyl)amino-3,S-dinitrophenyl] disulfide having a melting point of78-80 C.

Analysis: C H N O S M01. Wt.: 597; Calc.: C, 48.31; H, 5.40; N, 14.09;S, 10.75; Found: C, 48.46; H, 5.53; N, 13.88; S, 10.57. Mass spectraldata confirmed the disulfide structure and IR examination showed theabsence of the SCN function.

EXAMPLE 2 Bis[4-(n-butyl)ethylamino-3,S-dinitrophenyl] disulfide About10.4 g. (0.04 mole) of 4-chloro-3,5- dinitrophenyl thiocyanate weredissolved in about ml. of benzene and about 10.1 g. of n-butylethylaminewere added with stirring. The reaction and isolation of the product werecarried out as detailed in Example 1. About 11 g. of reddish-orangecrystals of bis[4-(n-butyl)ethylamino-3,S dinitrOphenyl] disulfide wereobtained with a melting point of 93-94 C.

Analysis: C H N O S,; Mol. Wt.: 597; Calc.: C, 48.31; H, 5.40; N, 14.09;S, 10.75; Found: C, 48.23; H, 5.31; N, 14.08; S, 10.85; Mass spectraland IR examination confirmed the disulfide structure and the absence ofthe SCN function, respectively.

EXAMPLE 3 Bis(4-hydroxy-3,S-dinitrophenyl) disulfide 1 N NO compound isbis[4-(n-butyl)ethylamino-3,5- dinitrophenyl] disulfide.

5. A compound according to claim 1 wherein the compound isbis(4-diallylamino-3,S-dinitrophenyl) disulfide.

6. A compound according to claim 1 wherein the compound isbis[4-di(2-propynylamino)-3,5- dinitrophenyl] disulfide.

UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION 3 ,725 M9 DatedApr 2 197 Patent No.

Inventor() William N. Cannon It is certified that error appears in theabove-identified patent and that said Letters Patent are herebycorrected as shown below:

Column 1, line 23 the last word in the line, of, is deleted and the wordisolated is subsTituted therefore.

Signed and sealed this 6th day of August 197b (SEAL) Attest:

MCCOY M. GIBSON, JR. 0. MARSHALL DANN Attesting Officer Commissioner ofPat ents

2. A compound according to claim 1 wherein the compound isbis(4-amino-3,5-dinitrophenyl) disulfide.
 3. A compound according toclaim 1 wherein the compound isbis(4-di(n-propyl)amino-3,5-dinitrophenyl) disulfide.
 4. A compoundaccording to claim 1 wherein the compound isbis(4-(n-butyl)ethylamino-3,5-dinitrophenyl) disulfide.
 5. A compoundaccording to claim 1 wherein the compound isbis(4-diallylamino-3,5-dinitrophenyl) disulfide.
 6. A compound accordingto claim 1 wherein the compound isbis(4-di(2-propynylamino)-3,5-dinitrophenyl) disulfide.